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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-11-17 - 1987-11-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Version / remarks:
revised Nov. 1984
Deviations:
no
GLP compliance:
yes
Remarks:
UD FDA (21 CFR 58) and uS ePA (40 CFR 160 and 40 CFR 792)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Appearance: Black powder
Bulk density: 0.21 g/mL
Solubility: Water: approximately 1 ppm; acetone: 0.81 g/100mL (20 °C); chloroform: 2 g/100mL (20 °C)
Storage: At ambient temperature in the dark in closed container
Stability: At least 14 days at 55 °C; poor in organic solvents

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
Six young adult albino rabbits of the New Zealand White strain, SPF-quality, were obtained from The Broekman Institute, Someren, The Netherlands. The animals arrived at the animal house November 9, 1987 and were approximately 10 weeks old at the start of the study. The animals were identified by means of ear labels and were individually housed in plastic cages with perforated floors. An Acclimatisation period of seven days was observed. The body weights of the animals, were measured one day before test substance administration. The animals were fed standard laboratory animal diet (100 g per day), obtained from Hope Farms, Woerden (LK-01, pellet diameter 4 mm), and had free access to decalcified tap-water.

ENVIRONMENTAL CONDITIONS
The animal room temperature was 20 - 21°C and the relative humidity 60 - 70 per cent. The artificial light sequence was 12 hours light, 12 hours dark.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
after 1, 24, 48 and 72 hours
Number of animals:
6
Details on study design:
TEST SYSTEM
One day before dose administration, the fur was removed from the dorsal flanks of the animals by clipping, exposing an area of the skin of approximately 10 cm x 10 cm. Prior to administration of the test substance the skin of all animals was inspected and found to be intact and normal.
The day of test substance administration was designated as day 0. Six portions of 0.5 gram of the test substance were transferred into glass vials; prior to administration each portion was moinstened with 0.5 mL Milli-RO water (Millipore corp., Bedford, Mass., USA). Immediately thereafter, each portion of the prepared test substance was evenly spread on a 6 cm2 gauze patsch of Metalline (Lohmann, FRG) and mounted on permeable tabe (Micropore, 3M, St. Paul, USA). This was applied to the left flank of each animal, the right flank being covered with the same dressing without test substance. Finally, the animals were wrapped in flexible bandage (Coban, 3M, St. Paul, USA). Exposure duration was 4 hours after which period the remaining test substance was removed, using a dry tissue and subsequently a tissue moistened with tap-water. However not all the test substance could remove from the skin: the skin looked slightly black.

OBSERVATION TIME POINTS
The exposed skin areas were examined for signs of erythema and oedema and the responses were scored approximately 60 minutes, and 24, 48 and 72 hours after removal of the patches. For reference the control site on the contralateral flank was used.

SCORING SYSTEM:
The following scoring system was used for grading of the skin irritation:
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to eschar formation
(injuries in depth) 4
Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite
raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and
extending beyond area of exposure) 4

Interpretatiton of the skin reactions
Primary irritation index Degree
0 not irriitating
< 2.0 slightly irritating
2.0 - 5.0 moderately irritating
> 5.0 severely irritating
The primary irritation index of a test material is calculated by combining the average skin irritation scores after 60 min, 24, 48 and 72 hours.
Note: if the interpretation based on the primary irritation index is not in accordance with the clinical appearance, the latter is taken for interpreting the skin reactions.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 60 min
Score:
0.02
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 60 min
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within:
Remarks:
24 h
Irritant / corrosive response data:
The test substance did not not cause any reaction to the skin, except with one animal. The skin of this animal showed very skight erythema 60 min after removal of the test substance only.
Other effects:
Signs of systemic intoxication were not observed in any of the rabibits.

Any other information on results incl. tables

The treated skin of all six animals was scored for erythema and oedema; the results are shown in Table 1.

Table 1: Primary Skin irritation scores in the rabbit (intact skin)
Test item
Rabbit #, sex and body weight Erythema / Eschar formation Oedema Values
Observations ST / 8*
60 min 24 hrs 48 hrs 72 hrs 7 d 14 d 21 d 60 min 24 hrs 48 hrs 72 hrs 7 d 14 d 21 d
3230
F
2386 g
0 0 0 0 - - - 0 0 0 0 - - - 0/8 = 0.00
3232
F
2248 g
0 0 0 0 - - - 0 0 0 0 - - - 0/8 = 0.00
3234
F
2427 g
0 0 0 0 - - - 0 0 0 0 - - - 0/8 = 0.00
3236
F
2370 g
0 0 0 0 - - - 0 0 0 0 - - - 0/8 = 0.00
3214
M
2086 g
0 0 0 0 - - - 0 0 0 0 - - - 0/8 = 0.00
3216
M
2190
1 0 0 0 - - - 0 0 0 0 - - - 1/8 = 0.13
Total = 0.13
Primary Irritation Index ( P. I. I.) = 0.13/6 = 0.02
Notes:
* Subtotal of scores for erythema and oedema of the first four observations according to the EPA calculatioon method.
- not measured

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
Based on the calculated primary irritation index of 0.02, the test substance would have to be considered as slightly irritating to the skin. However, from the very brief reaction in only one animal the interpretation 'practically non irritating' is preferred.
Executive summary:

The purpose of the study was to evaluate local irritating or corrosive effects of the test item on the rabbit skin following a single application of the test substance in an in vivo rabbit primary skin irritation/corrosion test according to US EPA FIFRA Guideline 81 -5 and in compliance with GLP.

The flank skin of 6 adult rabbits was exposed to 0.5 g of the test substance moistened with Willi-RO water for 4 hours using semi-occlusive dressing. The test substance did not cause any reaction to the skin, except for very slight erythema in one animal 60 min after removal of the dressings and disappearing within 24 hours. The primary skin irritation index amounted to 0.02. Based on these results the test substance should be considered as practically non irritating to the skin.